Researchers want to learn whether PhytoSERM, a supplement containing plant-derived compounds called phytoestrogens, may help support brain health and reduce menopause-related symptoms. The study will examine its effects on brain metabolism, cognitive function, hot flashes, sleep, and mood.

You may be eligible for this study if you meet the following criteria.

Inclusion Criteria:

• Experiencing hot flashes at least 5 times a day
• Perimenopausal, postmenopausal, or have had a hysterectomy, ablation, or IUD-related absence of periods
• Women ages 40-65
• Live in Arizona
• Willing and able to undergo Brain MRI (no non-removable metal in the body or claustrophobia) and PET scan
• Willing to travel to the Perseverance Research Center for 7 in-person visits

Exclusion Criteria:

• Currently using estrogen or progestin therapy (e.g., pills, patches, vaginal rings)
• Have experienced a cancer or tumor that was affected by estrogen (e.g., certain types of breast or uterine cancer)
• Significant medication changes in the past 2 weeks
• Use of nicotine or tobacco products (e.g., cigarettes, chewing tobacco, nicotine patch or gum) in the past 2 months

If you qualify and decide to participate, you will take part in a 28-week study with seven in-person visits, including a screening visit.

1. Complete a screening visit: Answer questions about your health, medical history, medications, and menopausal symptoms to determine whether you qualify.

2. Receive a study pill: You will be randomly assigned to take either PhytoSERM or a placebo (a pill that does not contain the active supplement) for the first three months. Neither you nor the study team will know which pill you receive during this period.

3. Continue taking PhytoSERM: During the final three months, all participants will receive PhytoSERM.

4. Complete health assessments: Throughout the study, you will undergo physical assessments, vital sign checks, blood and urine tests, an electrocardiogram (ECG), brain imaging scans (MRI and PET), and memory assessments and questionnaires. You will also wear a digital wristband.

Some participants may also choose to take part in an optional sub-study that examines how the body processes PhytoSERM.

Study visits will take place at the Perseverance Research Center in Scottsdale, Arizona, or at another study location that has not yet been confirmed.

Participants will receive $75 after completing each study visit, with the first payment provided after enrollment (following Visit 2). You may also receive additional compensation for completing certain study procedures:

• $100 after each PET scan

• $75 after each MRI

• $200 for participating in the optional pharmacokinetic sub-study

The maximum compensation for this study is $975. Participation in the optional pharmacokinetic sub-study is limited to 5-10 participants, and these participants will receive a maximum total compensation of $1,125.

Participants will also have access to many of the health assessment results collected during the study, such as blood work and PET scan results. Transportation assistance is not provided.

There is no cost for you to participate in our research study.